Severe headache trajectory following aneurysmal subarachnoid hemorrhage: the association with lower sodium levels.

BACKGROUND: A clinical hallmark of aneurysmal SAH (aSAH) is headache. Little is known about post-aSAH headache factors which may point to underlying mechanisms. In this study, we aimed to characterize the severity and trajectory of headaches in relation to clinical features of patients with aSAH. METHODS: This is a retrospective longitudinal study of adult patients admitted to an academic tertiary care center between 2012 and 2019 with aSAH who could verbalize pain scores. Factors recorded included demographics, aneurysm characteristics, analgesia, daily morning serum sodium concentration, and occurrence of vasospasm. Group-based trajectory modeling was used to identify headache pain trajectories, and clinical factors were compared between trajectories. RESULTS: Of 91 patients included in the analysis, mean age was 57 years and 20 (22%) were male. Headache score trajectories clustered into two groups: patients with mild-moderate and moderate-severe pain. Patients in the moderate-severe pain group were younger (P<0.05), received more opioid analgesia (P<0.001), and had lower sodium concentrations (P<0.001) than patients in the mild-moderate pain group. CONCLUSION: We identified two distinct post-aSAH headache pain trajectory cohorts and identified an association with age, analgesia, and sodium levels. Future prospective studies considering sodium homeostasis and volume status under standardized analgesic regimens are warranted.

Corneal Reflex Testing in the Evaluation of a Comatose Patient: An Ode to Precise Semiology and Examination Skills.

BACKGROUND/OBJECTIVE: The corneal reflex assesses the integrity of the trigeminal and facial cranial nerves. This brainstem reflex is fundamental in neuroprognostication after cardiac arrest and in brain death determination. We sought to investigate corneal reflex testing methods among neurologists and general critical care providers in the context of neuroprognostication following cardiac arrest. METHODS: This is an international cross-sectional study disseminated to members of the Neurocritical Care Society, Society of Critical Care Medicine, and American Academy of Neurology. We utilized an open Web-based survey (Qualtrics®, Provo, UT, USA) to disseminate 26 questions regarding neuroprognostication practices following cardiac arrest, in which 3 questions pertained to corneal reflex testing. Descriptive statistical measures were used, and subgroup analyses performed between neurologists and non-neurologists. Questions were not mandatory; therefore, the percentages were relative to the number of respondents for each question. RESULTS: There were 959 respondents in total. Physicians comprised 85.1% of practitioners (762 out of 895), of which 55% (419) identified themselves as non-neurologists and 45% (343) as neurologists. Among physicians, 85.9% (608 out of 708) deemed corneal reflex relevant for prognostication following cardiac arrest (neurologists 84.4% versus non-neurologists 87.0%). A variety of techniques were employed for corneal reflex testing, the most common being "light cotton touch" (59.2%), followed by "cotton-tipped applicator with pressure" (23.9%), "saline or water squirt" (15.9%), and "puff of air" (1.0%). There were no significant differences in the methods for testing between neurologists and non-neurologists (p = 0.52). The location of stimulus application was variable, and 26.1% of physicians (148/567) apply the stimulus on the temporal conjunctiva rather than on the cornea itself. CONCLUSIONS: Corneal reflex testing remains a cornerstone of the coma exam and is commonly used in neuroprognostication of unconscious cardiac arrest survivors and in brain death determination. A wide variability of techniques is noted among practitioners, including some that may provide suboptimal stimulation of corneal nerve endings. Imprecise testing in this setting may lead to inaccuracies in critical settings, which carries significant consequences such as guiding decisions of care limitations, misdiagnosis of brain death, and loss of public trust.

Intracerebral Hemorrhage Location and Functional Outcomes of Patients: A Systematic Literature Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) has the highest mortality rate among all strokes. While ICH location, lobar versus non-lobar, has been established as a predictor of mortality, less is known regarding the relationship between more specific ICH locations and functional outcome. This review summarizes current work studying how ICH location affects outcome, with an emphasis on how studies designate regions of interest. METHODS: A systematic search of the OVID database for relevant studies was conducted during August 2015. Studies containing an analysis of functional outcome by ICH location or laterality were included. As permitted, the effect size of individual studies was standardized within a meta-analysis. RESULTS: Thirty-seven studies met the inclusion criteria, the majority of which followed outcome at 3 months. Most studies found better outcomes on the Modified Rankin Scale (mRS) or Glasgow Outcome Score (GOS) with lobar compared to deep ICHs. While most aggregated deep structures for analysis, some studies found poorer outcomes for thalamic ICH in particular. Over half of the studies did not have specific methodological considerations for location designations, including blinding or validation. CONCLUSIONS: Multiple studies have examined motor-centric outcomes, with few studies examining quality of life (QoL) or cognition. Better functional outcomes have been suggested for lobar versus non-lobar ICH; few studies attempted finer topographic comparisons. This study highlights the need for improved reporting in ICH outcomes research, including a detailed description of hemorrhage location, reporting of the full range of functional outcome scales, and inclusion of cognitive and QoL outcomes.

Early head CT in post-cardiac arrest patients: A helpful tool or contributor to self-fulfilling prophecy?

OBJECTIVE: Neuroprognostication guidelines suggest that early head computed tomography (HCT) might be useful in the evaluation of cardiac arrest (CA) patients following return of spontaneous circulation. We aimed to determine the impact of early HCT, performed within the first 6 h following CA, on decision-making following resuscitation. METHODS: We identified a cohort of initially unconscious post-CA patients at a tertiary care academic medical center from 2012 to 2017. Variables pertaining to demographics, CA details, post-CA care, including neuroimaging and neurophysiologic testing, were abstracted retrospectively from the electronic medical records. Changes in management resulting from HCT findings were recorded. Blinded board-certified neurointensivists adjudicated HCT findings related to hypoxic-ischemic brain injury (HIBI) burden. The gray-white matter ratio (GWR) was also calculated. RESULTS: Of 302 patients, 182 (60.2%) underwent HCT within six hours of CA (early HCT group). Approximately 1 in 4 early HCTs were abnormal (most commonly HIBI changes; 78.7%, n = 37), which resulted in a change in management in nearly half of cases (46.8%, n = 22). The most common changes in management were de-escalation in care [including transition to do not resuscitate status), withholding targeted temperature management, and withdrawal of life sustaining therapy (WLST)]. In cases with radiographic HIBI, mean [standard deviation] GWR was lower (1.20 [0.10] vs 1.30 [0.09], P < 0.001) and progression to brain death was higher (44.4% vs 2.9%; P < 0.001). The inter-rater reliability (IRR) of early HCT to determine presence of HIBI between radiology and three neurointensivists had a wide range (κ 0.13-0.66). CONCLUSION: Early HCT identified abnormalities in 25% of cases and frequently influenced therapeutic decisions. Neuroimaging interpretation discrepancies between radiology and neurointensivists are common and agreement on severity of HIBI on early HCT is poor (k 0.11).

Postcardiac Arrest Neuroprognostication Practices: A Survey of Brazilian Physicians.

End-of-life care and decisions on withdrawal of life-sustaining therapies vary across countries, which may affect the feasibility of future multicenter cardiac arrest trials. In Brazil, withdrawal of life-sustaining therapy is reportedly uncommon, allowing the natural history of postcardiac arrest hypoxic-ischemic brain injury to present itself. We aimed to characterize approaches to neuroprognostication of cardiac arrest survivors among physicians in Brazil. DESIGN: Cross-sectional study. SETTING: Between August 2, 2019, and July 31, 2020, we distributed a web-based survey to physicians practicing in Brazil. SUBJECTS: Physicians practicing in Brazil and members of the Brazilian Association of Neurointensive Care, who care for patients resuscitated following cardiac arrest. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Responses from 185 physicians were obtained. Pupillary reflexes, corneal reflexes, and motor responses were considered critical to prognostication, whereas neuroimaging and electroencephalography were also regarded as important. For patients without targeted temperature management, absent pupillary and corneal reflexes at 24 hours postarrest were considered strongly predictive of poor neurologic outcome by 31.8% and 33.0%, respectively. For targeted temperature management-treated patients, absent pupillary and corneal reflexes at 24-hour postrewarming were considered prognostic by 22.9% and 20.0%, respectively. Physicians felt comfortable making definitive prognostic recommendations at day 6 postarrest or later (34.2%) for nontargeted temperature management-treated patients, and at day 6 postrewarming (20.4%) for targeted temperature management-treated patients. Over 90% believed that improving neuroprognostic accuracy would affect end-of-life decision-making. CONCLUSIONS: There is significant variability in neuroprognostic approaches to postcardiac arrest patients and timing of prognostic studies among Brazilian physicians, with practices frequently deviating from current guidelines, underscoring a need for greater neuroprognostic accuracy. Nearly all physicians believed that improving neuroprognostication will impact end-of-life decision-making. Given the tendency to delay prognostic recommendations while using similar neuroprognostic tools, Brazil offers a unique cohort in which to examine the natural history of hypoxic-ischemic brain injury in future studies.

Distinct predictive values of current neuroprognostic guidelines in post-cardiac arrest patients.

PURPOSE: To assess the performance of neuroprognostic guidelines proposed by the American Academy of Neurology (AAN), European Resuscitation Council/European Society of Intensive Care Medicine (ERC/ESICM), and American Heart Association (AHA) in predicting outcomes of patients who remain unconscious after cardiac arrest. METHODS: We retrospectively identified a cohort of unconscious post-cardiac arrest patients at a single tertiary care centre from 2011 to 2017 and reviewed hospital records for clinical, radiographic, electrophysiologic, and biochemical findings. Outcomes at discharge and 6 months post-arrest were abstracted and dichotomized as good (Cerebral Performance Category (CPC) scores of 1-2) versus poor (CPC 3-5). Outcomes predicted by current guidelines were compared to actual outcomes, with false positive rate (FPR) used as a measure of predictive value. RESULTS: Of 226 patients, 36% survived to discharge, including 24 with good outcomes; 52% had withdrawal of life-sustaining therapies (WLST) during hospitalization. The AAN guideline yielded discharge and 6-month FPR of 8% and 15%, respectively. In contrast, the ERC/ESICM had a FPR of 0% at both discharge and 6 months. The AHA predictors had variable specificities, with diffuse hypoxic-ischaemic injury on MRI performing especially poorly (FPR 12%) at both discharge and 6 months. CONCLUSIONS: Though each guideline had components that performed well, only the ERC/ESICM guideline yielded a 0% FPR. Amongst the AAN and AHA guidelines, false positives emerged more readily at 6 months, reflective of continuing recovery after discharge, even in a cohort inevitably biased by WLST. Further assessment of predictive modalities is needed to improve neuroprognostic accuracy.

Differential outcomes following successful resuscitation in cardiac arrest due to drug overdose.

BACKGROUND: Data pertaining to clinical characteristics and outcomes of cardiac arrest (CA) due to drug overdose (ODCA) are limited. We hypothesized that patients with ODCA would have binary outcomes (brain death or functional recovery) compared to patients in whom CA was due to another etiology. METHODS: We performed a retrospective analysis of CA cases from a single academic institution from 2012 to 2017. ODCA cases were ascertained by admission notes strongly suggestive of OD or positive toxicology screens not explained by medication administration. Clinical characteristics and outcomes were extracted from medical records, and regression modeling was used to compare ODCA and non-ODCA patients. RESULTS: Of the 300 CA cases in this analysis, 28 (9%) were attributed to drug overdose, with opioids accounting for 54%. ODCA patients were younger, had fewer comorbidities, were less likely to have witnessed arrests or bystander cardiopulmonary resuscitation, and had longer downtimes. Inpatient mortality did not differ between cohorts (79% ODCA, 73% non-ODCA, p = 0.66), but ODCA was associated with higher rates of brain death (43%, 6%, p < 0.001). Of patients who survived to discharge, there was no difference in the likelihood of favorable neurological recovery, defined as Cerebral Performance Category score of 1-2 (7%, 7%, p = 1.00) or modified Rankin Scale score of 0-3 (7%, 9%, p = 1.00). CONCLUSIONS: Despite similar neurological recovery and survival rates to hospital discharge, ODCA patients were more likely than non-ODCA patients to progress to brain death. Larger prospective studies analyzing ODCA are needed to better understand potential treatment options and prognostic tools in this cohort.

Expression of gC1q-R/p33 and its major ligands in human atherosclerotic lesions.

A growing body of evidence supports the hypothesis that atherosclerosis has an inflammatory component, and that immune mechanisms, including complement activation, are likely to be involved. gC1q-R/p33 (gC1q-R) is a multifunctional and multicompartmental cellular protein, which is postulated to play a role in inflammation and thrombosis by interacting with C1q and high molecular weight kininogen (HK). To examine the expression of gC1q-R and its major ligands, C1q and HK, in human atherosclerotic lesions, sections of carotid arteries removed during endarterectomy and coronary arteries obtained at autopsy were stained with specific polyclonal or monoclonal antibodies. Control sections were stained with irrelevant rabbit IgG or isotype matched murine monoclonal antibody (MOPC), respectively. Tissue sections were counterstained with hematoxylin and examined by light microscopy. Specific staining for gC1q-R, C1q, and HK was observed in and around atherosclerotic lesions. In contrast to control antibodies, antibodies directed against gC1q-R reacted with endothelial cells, foam cells, smooth muscle cells, and inflammatory cells present in the intima and media of atherosclerotic lesions. In addition, the necrotic central core of advanced lesions with calcifications, fibrin, and lipids, stained intensely for gC1q-R, and negligibly with control antibodies. HK demonstrated a similar staining pattern, whereas C1q was most heavily expressed in the fibrous cap and necrotic core of atherosclerotic lesions. The localization of gC1q-R and its ligands C1q and HK in atherosclerotic lesions, and the previously described ability of gC1q-R to modulate complement, kinin, and coagulation cascades, suggest that gC1q-R may play an important role in promoting inflammation and thrombosis in atherosclerotic lesions.